May be considered in central post-stroke pain or spinal cord injury with incomplete cord lesion and brush-induced allodynia only if all other treatments fail

Cannabinoids

Eg Tetrahydrocannabinol, Cannabidiol

May be considered in central pain in multiple sclerosis only if all other treatments fail

Painful Diabetic Peripheral Neuropathy

1st-Line Agents

Anticonvulsants

Gabapentin has effective pain relief for patients with diabetic peripheral neuropathy; similar efficacy as Amitriptyline but with a better side effect profile

A recent study on Gabapentin and Nortriptyline use for diabetic peripheral neuropathy or postherpetic neuralgia, showed significantly lower pain scores in the combination phase than for either treatment alone; Gabapentin monotherapy and Nortriptyline monotherapy were similar in efficacy

Recommended by European Federation of Neurological Societies (EFNS) and International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) as 2nd-line treatment except for those with acute exacerbation of diabetic peripheral neuropathy, in which case it can be considered as 1st-line option

Tramadol and Tramadol/Paracetamol combination are effective in reducing pain due to diabetes

Use with caution in the elderly because of risk of confusion; it is also associated with increased risk of serotonin syndrome when used together with serotonergic drugs

Lidocaine (Topical)

As per 2015 recommendations from International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG), Lidocaine patches can be a 2nd-line treatment due to its safety proﬁle and patient preferences

Small randomized or open-label trials have shown the efficacy of topical 5% Lidocaine transdermal patches for pain relief in patients with diabetic peripheral neuropathy, with minimal adverse events; significant improvement in ongoing pain, intensity of allodynia and quality-of-life measures have also been noted

Capsaicin (Topical)

It has been proposed by International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) that Capsaicin patches can be a 2nd-line treatment for peripheral neuropathy

Depletes stores of substance P from sensory nerve endings, reducing or abolishing transmission of painful stimuli from the peripheral nerve fibers to the higher centers

Patient needs to be willing to apply 3-4 times daily and may experience initial skin irritation which typically improves in 1-2 weeks

Studies have shown that it decreases pain, paresthesias and numbness, and has a favorable safety profile

Benfotiamine

Lipid-soluble thiamine derivative that studies show to have improved neuropathic pain in patients with diabetic neuropathy as being a transketolase activator and inhibitor of alternative metabolic pathways implicated in the pathogenesis of hyperglycemia-induced vascular damage

Tapentadol

An opioid with noradrenaline reuptake inhibition with low affinity for the mu opioid receptor

Gabapentin and Pregabalin have established efficacy against post herpetic neuralgia

1st-line agent for post herpetic neuralgia, especially in the elderly in whom tricyclic antidepressants are not well-tolerated

Gabapentin produces significant pain relief and improvement in measures of quality of life and mood

Pregabalin has been shown to significantly decrease pain and improve sleep in randomized placebo-controlled trials

Tricyclic Antidepressants

Amitriptyline, Desipramine, Nortriptyline and Maprotiline have been used successfully with Amitriptyline as the most widely used tricyclic antidepressants for post herpetic neuralgia

Nortriptyline has been shown to be as effective as Amitriptyline but better tolerated

Many controlled trials have shown the efficacy of tricyclic antidepressants in post herpetic neuralgia

2nd-line Agents

Lidocaine (Topical)

Generally recommended as 2nd-line treatment for postherpetic neuralgia by International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) due to low quality of evidence

Recommended as 1st-line treatment by International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) for the elderly frail patients, in whom there are concerns for central nervous system adverse reactions from oral medications

Five randomized placebo-controlled trials in postherpetic neuralgia supported the efficacy of Lidocaine patches with brush-induced allodynia

Lidocaine gel (5%) has been shown to give significant pain relief in postherpetic neuralgia for up to 8 hours

Capsaicin (Topical)

Recommended as 2nd-line treatment for postherpetic neuralgia by International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) due to relatively small eﬀective size

Provides significant pain relief but patient response can be delayed

Discomfort and burning sensation may limit patient compliance

Tramadol

A weak opioid and a mixed serotonin-noradrenaline reuptake inhibitor found in studies to be an alternative if ﬁrst-line oral monotherapies are ineﬀective

Recommended as 2nd-line treatment for postherpetic neuralgia by International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) due to potential safety concerns

3rd-Line Agents

Opioids

Generally recommended as 3rd-line treatment for postherpetic neuralgia by International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) due to abuse potential and side eﬀects that include endocrine eﬀects

Oxycodone, Morphine and Methadone have similar efficacy in postherpetic neuralgia compared to tricyclic antidepressants but these are associated with frequent discontinuation because of adverse events

It has been recommended as 3rd-line treatment for postherpetic neuralgia by International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) due to weak quality of evidence thus it is only used in refractory cases

If adequate pain control is not achieved using pharmacological agents discussed above, consider expert referral to a pain medicine specialist for alternative therapy

Drug of choice for trigeminal neuralgia but efficacy may be compromised by poor tolerability and pharmacokinetic interactions

Randomized placebo-controlled trials have shown reduction in frequency and intensity of painful paroxysms and equal efficacy for spontaneous and trigger-evoked attacks

Oxcarbazepine

Typically better tolerated than Carbamazepine due to decreased potential for drug interactions

Two randomized placebo-controlled trials found similar efficacy of Oxcarbazepine with Carbamazepine on number of attacks and global assessment

If refractory to Carbamazepine and Oxcarbazepine, 2nd-line agents may be added to treatment regimen for trigeminal neuralgia

2nd-line Agents

Baclofen has been reported in a study to be superior to placebo in reducing the number of painful paroxysms in trigeminal neuralgia

Lamotrigine has been reported in a study to be efficacious in trigeminal neuralgia and may also be effective as add-on therapy

Other anticonvulsants (eg Clonazepam, Gabapentin, Phenytoin and Valproate) have been suggested in small open-label studies to have therapeutic benefit for trigeminal neuralgia but evidence remains insufficient to support or refute their efficacy

Non-Pharmacological Therapy

Central Neuropathic Pain

Psychological Approaches

Psychological or behavioral therapy may of benefit in some patients

Painful Diabetic Peripheral Neuropathy (DPN)

Optimize Glycemic Control

Tight glucose control in type 1 diabetes mellitus patients helps to delay the onset of diabetic polyneuropathy and helps to slow the progression of the disease

The benefits of intensive insulin therapy usually outweigh the risks

It is generally agreed that any improvement in glycemic control in type 2 diabetes mellitus patients is beneficial

Use tight glucose control in the elderly with caution as they are more susceptible to the effects of hypoglycemia

Proper Foot Care

Patients should inspect their feet daily, use proper foot hygiene and wear proper fitting socks/hosiery that is changed daily

Footwear

Patients with neuropathy may benefit from well-fitted walking shoes or athletic shoes

If patient has evidence of increased plantar pressure then their footwear should cushion and redistribute pressure

Expert referral if patient suffers trauma, cellulitis or acute ischemia of the foot

Psychological Approaches

Cognitive behavioral therapy may of benefit in reducing pain severity and interference in patients with painful diabetic neuropathy as per recent pilot randomized controlled study

Alternative Therapies

Physiotherapy has been reported to provide pain relief in some patients

Acupuncture has minimal but not insignificant risks

May relieve pain and/or reduce the need for pain medications in selected patients

Transcutaneous Electrical Nerve Stimulation

Mild electrical stimulation through the application of surface electrodes over the painful area generates heat that relieves stiffness and improves mobility

Among offspring of parents with bipolar disorder (OBP), resting-state functional connectivity (rsFC) between left inferior frontal gyrus (IFG) and clusters in the left insula (LINS) may be a risk marker for the development of bipolar disorder, suggests a study.

Exposure to ambient pesticides within 2,000 m of the mother’s residence during pregnancy increases the risk of autism spectrum disorder (ASD) in offspring, suggests a study. Moreover, risks for ASD with comorbid intellectual disability are further increased when infant is exposed to pesticides.